Recently, the National Bureau of Statistics of China (NBS) revealed that the Purchasing Manager Index (PMI) picked up sharply in March. Manufacturing, non-manufacturing and comprehensive PMI increased to above 52%, and 96.6% of large and medium-sized enterprises have resumed work. Since the outbreak of COVID-19 in December, the Chinese government has implemented strict measures to contain the spread of the virus. As Wuhan lifts its 76-day lockdown, China is leading the global post-pandemic recovery. However, since COVID-19 is highly contagious, the importance of maintaining regular epidemic prevention and control measures should not be overlooked before effective drugs and vaccines reach the public. In this issue of the COVID-19 column, we will discuss hot topics including how the COVID-19 pandemic is expected to develop and how should people prepare in the post-outbreak era.
How will the COVID-19 Pandemic Develop After the Major Breakout?
Generally, the development of the epidemic can be divided into five stages, from the identification of a small number of cases to the sustained spread and eventually to the stabilization and decline. A recent report issued by McKinsey suggested that Asian countries, such as China, Japan and South Korea, would reach the stabilization and decline stage sooner, while the cases in Europe and America are expected to peak between April and May.
With effective social distancing measures, sufficient testing capacity, and effective medical supports in place, we have the reason to believe that the trend of exponentially growing cases worldwide would not last for too long. However, whether there will be recurring outbreaks after this major one is a concerning question that everyone needs to consider beforehand. Although preliminary evidence suggests that the activity of COVID-19 is reduced under high temperature, it remains unclear whether this suggests that the epidemic will be seasonal, and the transmission will be reduced in summer.
Therefore, in countries where the outbreak is under control, the public should bear in mind the possibility that COVID-19 may linger for the rest of the year, imported cases from other countries may continue to increase, and control measures may even restart if necessary. Nevertheless, it should be acknowledged that countries that have successfully controlled the outbreak have gained considerable experience in determining and implementing effective measures to timely mitigate any possible risks that would lead to another outbreak in the future.
Will the COVID-19 virus disappear from or coexist with the human population after the major outbreak?
According to the current research and experience, an epidemic may potentially end in two ways as follows. A virus that is highly pathogenic and fatal is unable to coexist with its host, and thus is likely to disappear after a major outbreak. On the other hand, a virus that is highly infectious but less fatal and pathogenic is more likely to co-exist with the host in the long-term. The SARS virus is a typical example of the former. Although SARS caused severe symptoms and death in a large proportion of the infected patients, the epidemic was quickly under control once the transmission was effectively contained. In contrast, current evidence that describes the transmissibility and lethality of the COVID-19 virus suggests it may belong to the other category - it is highly infectious, although it is quite lethal compared to flu, the fatality rate is significantly lower than that of SARS. Although it remains unclear whether the COVID-19 virus will stay with the human population for a long time, we should recognize such a possibility and plan precautionary measures accordingly.
Infectivity and Fatality of Influenza Virus, COVID-19, and SARS
How long before the impact of COVID-19 on human society is minimized?
For now, the extensive practice of social distancing and travel restrictions are the most effective measures to curb the epidemic. However, these measures also compromise economic development and thus cannot be maintained forever. As the first country that has successfully controlled the outbreak, China is adopting a gradual approach when lifting its restrictions and control measures, thereby balancing the risk of another outbreak and the demand for economic recovery. This paradigm may can a meaningful reference for other countries as they enter the post-outbreak period. In the long term, there are two ways to put an end to the epidemic: a vaccine or the achievement of herd immunity.
Currently, there are 115 candidate vaccines for COVID-19 under development worldwide, of which five have entered the clinical development stage. Several global pharmaceutical companies with extensive experience in vaccine production and supply, such as Sanofi, Pfizer, Janssen Pharmaceutical, and GlaxoSmithKline, have also joined the development. However, with the most optimistic estimates, it will take at least 12 to 18 months for the vaccine to be put into use. Even though, it is possible that, during the initial period, the use of the vaccine is restricted to under specific circumstances only rather than for the general public.
On average, vaccine development could take more than 10 years. Although current R&D efforts are advancing at an unprecedented speed, there is simply no shortcut to take for the meticulous safety and effectiveness evaluation required at each step-in vaccine development. Besides the challenges at the R&D stage, regulatory procedures will need to revise, production capacity must be ensured, and the limited resources will need to be rationally allocated. These will all require the joint coordination and cooperation of vaccine developers, regulatory agencies, policymakers, and governments. At the same time, the phenomenon known as ‘antigen drift’, which is posing challenges to developing an effective flu vaccine, may also affect the development of the COVID-19 vaccine.
Antigenic drift is a kind of genetic variation in viruses, arising by the accumulation of mutations in the virus genes that code for virus-surface proteins, which serves as a label to be recognized by the host immune system. If antigen drift occurs, the mutated virus may evade the detection of the immune system, since there is no ‘memory’ formed against the new form of the virus.
Mutations in RNA viruses, which include coronaviruses, occur frequently because the virus' replication machinery does not have a proofreading mechanism. For the previous epidemics caused by coronaviruses, namely SARS and MERS, vaccines were not able to be developed in a short time, and in fact, not until today. Therefore, it is reasonable to expect that the vaccine development for COVID-19 will face the same challenge. In addition, it should be recognized that even if there is a vaccine that is initially effective, antigen drift could still render it ineffective. Taking the flu vaccine as an example, current vaccination, at its best, is only effective against the main strain of influenza virus in a certain year. It cannot protect one against all strains of the virus in a certain year, nor can it protect one from being infected next year.
Herd immunity refers to a form of protection from infectious disease that occurs when a large percentage of a population has become immune to an infection. The higher the proportion of individuals with immunity, the less likely a susceptible individual contact with an infected individual. When the immunized population reaches above 85%, the virus will wane and disappear as there are no sufficient hosts and contacts between infectable hosts to support the spread. Vaccination is the most effective way to achieve herd immunity. For example, smallpox and polio have been largely exterminated through extensive vaccination, and almost no new cases have been identified in developed countries.
Recently, herd immunity was brought into sight by the U.K. government, which proposed in March to control the COVID-19 virus using such concept, but through infection and not vaccination. Although the idea of combating COVID-19 with herd immunity is valid, the costs and consequences of achieving it through infection are too much. Current data suggests that the R0 value of COVID19 is between 2 to 3 - that is, one infected person can spread to 2 to 3 people. On this basis, at least 82% of the U.K. population will need to be infected to achieve herd immunity. The research conducted by the University of Minnesota and published in Nature suggests that 60% of those infected by COVID-19 are asymptomatic or with mild symptoms, which suggests that the rest experience severe symptoms. Additionally, 1 to 3% percent of infected patients die. These numbers are terrifying when put into the context of the entire U.K. population, and allowing this to happen is essentially surrendering to the virus.
Professor Nanshan Zhong, a prestigious Chinese epidemiologist commented that ‘Going backward a hundred years, achieving herd immunity through infection was an option when humans simply did not have a better way to go. They could only let the virus infect, and it is a natural consequence that people who survived got immunized.” Certainly, with the advancements in technology and human society, rather than let the virus infect, the best strategy to minimize sacrifices and losses is to implement effective intervention measures to contain the virus as much as possible while vaccines and drugs are being developed.
What Does It Mean for Us?
First, there is no need to panic. As the first country to successfully control the COVID-19 epidemic, China has gained a lot of experience along the way. While the government continues to implement necessary measures, the general public is also ready to practice essential measures at an individual level to protect others and one’s own health. Therefore, in the short term, new cases in China will be contained in a small portion of the population, and the risk for another major outbreak is low. Besides, China's successful experience in controlling the epidemic will be meaningful for the European and American countries both in the current outbreak and in the post-outbreak period in the near future.
Although the COVID-19 virus may coexist with the human population in the long term, it will need to continuously reduce its pathogenicity and lethality, potentially through mutation, to achieve better host adaptability. Therefore, its impact on human society will gradually decline to a level similar to the flu. Taking the SARS virus as an example, research shows that the SARS antibody is still detected in roughly 6% of the population at 17 years after its outbreak, revealing that the SARS virus has not completely disappeared, but it has neither another major outbreak. As drugs and vaccines are being developed at unprecedented speed, the COVID-19 virus may as well disappear from human society just like all those once frightening viruses did.
At present, people should bear in mind that they are still in the late but not the end stage of the outbreak. As the vaccine not yet available and the major population remain unimmunized, all intervention measures are only effective if each individual complies and practice regular precautionary measures to protects themselves. Wearing masks, washing hands, and disinfecting crowded spaces should be regularly practiced as if the outbreak is still ongoing. At the same time, maintaining a healthy diet, exercising, and avoiding stress will all be helpful in strengthening immunity. Besides, do not believe in any off-label indications directed to treating or preventing COVID-19 infection unless it is suggested by professionals. If you don’t feel well, seek medical help immediately; if you are infected, only valid medical supports and life support systems can minimize the damages and losses.